The analysis of genetic information will be a central requirement for all of the projects described in this grant proposal. The Genomics Core will provide high-throughput facilities for DNA sequencing, mRNA expression analysis, and single-nucleotide polymorphism (SNP) detection at the Institute for Systems Biology (ISB). The sequencing core is a high-capacity, fully automated facility developed to manage sequence analysis from eDNA libraries, BAC libraries, or PCR products in a cost-effective manner. The in-house array production and analysis facility at the ISB will be used to quantitate mRNA expression of genes involved in sepsis. This facility is currently producing high-density arrays (up to 40,000 genes per array) as well as customized arrays with select sets of genes. The facility is automated to analyze multiple arrays from clinical samples, which will be necessary to correlate in vitro data with clinical data. SNP technology has been established to both discover new SNPs as well as provide high-throughput SNP detection from multiple patient samples. SNPs are discovered by a heteroduplex mismatch detection method that has been adapted for use with arrays in a high-throughput manner. Known SNPs are detected by hybridization of an allele-specific oligonucleotide probe to an array of PCR products amplified from patient's genomic DNA.